Smith-Magenis syndrome (SMS), a probable contiguous gene syndrome due to del 17p11.2, is associated with a distinct phenotype of characteristic physical features, developmental delay, speech delay with or without associated hearing loss, clinical signs of peripheral neuropathy, and neurobehavioral problems including sleep disturbance, outbursts and self-injurious behaviors. First reported by Smith et al. in 1982, over 100 individuals representing a diversity of ethnic backgrounds have been identified with the syndrome worldwide. While the clinical findings have been fairly well delineated, specific oral-motor, voice and otolaryngologic findings related to speech dysfunction warrant further refinement. Baseline data was collected on 14 children (6M/8F) with SMS, ranging in age from 9 months to 16 years seen under Protocol 95HG0010 by an interdisciplinary team of researchers. All were evaluated as part of a SMS Multidisciplinary Clinic held at NIH in March, 1997 prior to the 1st National SMS Conference March 15-17, 1997. Craniofacial measurements using objective Z-score pattern analysis supports previous subjective impressions of facial changes. Speech impairment was exhibited in 10 of 12 verbal children; hearing loss in 9/14. Lingual findings and one or more laryngeal findings were demonstrated in all 14 patients. Structural vocal fold abnormalities were seen in all but the youngest subject. These findings provide a physiologic explanation for the functional impairment in voice and speech previously reported in SMS and suggest a possible gene in the SMS critical region involved in development of laryngeal and pharyngeal structures. Elevated LDL cholesterol observed in 8 of 14 subjects is intriguing given that the gene for sterol regulatory element binding protein (SREBF1) maps to 17p11.2. A specific protocol to examine the natural history and pathophysiology of SMS across the lifespan is currently planned.